Transcriptomic Mechanisms of Formation and Persistence of Synapse Specific Long-Term Memory

突触特异性长期记忆形成和持续的转录组机制

• 批准号: 10609651
• 负责人: Sathyanarayanan V Puthanveettil
• 金额: $ 23.18万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-12 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10609651
• 关键词: Transcriptomic; Mechanisms; Formation; Persistence; Synapse

PROJECT SUMMARY Long-term memory (LTM) storage requires remodeling of pre-existing synapses and formation of new ones. While the necessity of transcription in the temporal phases of LTM such as formation and persistence has been described, we lack comprehensive information on how gene expression changes in a neural circuitry mediate the formation and persistence of LTM. In any of the animal models of learning, we do not know what components of the transcriptomes are recruited specifically in pre- or post-synaptic neurons for mediating the formation and persistence of LTM. Particularly we know very little about the gene expression changes required for the persistence of LTM. Lack of this knowledge is a critical barrier for deciphering the molecular underpinnings of synapse specificity and LTM. The central hypothesis of this proposal is that coordinated regulation of the pre- and the post-synaptic neuronal transcriptome mediate the formation and persistence of synapse specific LTM. We propose to test this hypothesis using the well-characterized neural circuitry of gill-withdrawal reflex (GWR) of the marine snail, Aplysia californica. Specifically, using a modified bifurcated sensory neuron-motor neuron culture, we will assess the changes in the subcellular transcriptome of pre-synaptic sensory neurons and post-synaptic motor neurons during the formation and persistence of the synapse specific LTM. Furthermore, the role of molecular motor kinesin mediated transport of RNAs from the cell body to synapses in synapse specific LTM will be determined. We anticipate that these experiments will facilitate the decoding of the gene expression program for the formation and persistence of LTM in components of a defined neural circuitry. Furthermore, our studies are expected to produce a ground- breaking impact on the basic biology of synapse specific LTM as well as to facilitate identification of novel candidates for the development of therapeutics for memory disorders.

项目摘要 长期记忆（LTM）存储需要重塑预先存在的突触和形成新的突触。 一个而在LTM的形成和持续等时间阶段转录的必要性 虽然已经描述过，但我们缺乏关于神经回路中基因表达如何变化的全面信息。 介导LTM的形成和持久性。在任何动物学习模型中，我们都不知道 转录组的组分特异性地在突触前或突触后神经元中募集，用于介导突触后的突触后神经元的突触后反应。 LTM的形成和持久性。特别是我们对基因表达的变化知之甚少 对于LTM的持久性是必需的。缺乏这方面的知识是破译分子的关键障碍 突触特异性和LTM的基础。这一建议的核心假设是， 突触前和突触后神经元转录组的调节介导了突触后神经元转录组的形成， 突触特异性LTM的持久性。我们建议使用表征良好的 加利福尼亚海蜗牛回鳃反射的神经回路。具体来说，使用 改良的分叉感觉神经元-运动神经元培养，我们将评估亚细胞的变化， 突触前感觉神经元和突触后运动神经元的转录组， 突触特异性LTM的持久性。此外，分子运动因子在介导的转运中的作用 将确定突触特异性LTM中RNA从细胞体到突触的量。我们预计， 实验将有助于解码基因表达程序的形成和持续， LTM在定义的神经回路的组件中。此外，我们的研究预计将产生一个地面- 突破突触特异性LTM的基础生物学的影响，以及促进新的识别 用于开发记忆障碍疗法的候选人。